| Description |
Rheumatoid arthritis (RA) is a chronic, progressive inflammatory disease which initially strikes the joints at the extremities, resulting in pain, swelling, stiffness, and loss of mobility, then later affects the larger joints. As the disease advances irreversible joint damage occurs, leading to deformity and loss of independence. Severe, long term RA quite frequently generates systemic complications, often made manifest by vascular maladies, organ damage, and, in some cases, death. It is clear that genetic factors are involved in the development of RA. However, despite evidence of genetic factors in the development of RA, there is little doubt that other, ill-defined factors are involved. The joint and tissue damage done by rheumatoid arthritis are affected by the patient's own immune system. However, no causative agent or agents have ever been clearly defined that trigger RA in an individual. Since the cause of RA and the exact mechanisms of disease pathogenesis remain unknown, the development of effective, long-term therapies for rheumatoid arthritis remains exceedingly difficult. Therefore, the clear definition of the triggers of RA and the elucidation of the pathways of immune system involvement of the pathogenesis of the disease are of utmost importance. It is believed that the pathogenesis associated with rheumatoid arthritis is mediated by the activities of CD4+ T-cells. Numerous studies have focused on the T-cell receptor repertoire of rheumatoid arthritis patients. It is believed that if RA results from a T-cell response to certain definable autoantigens or foreign antigens or superantigens, a subset of T-cell receptor Vbeta families should be expressed at abnormally high levels. Analysis of the T-cell receptor mRNA transcripts has been performed using RT-PCR. Results from these analyses have been conflicting. No consistently elevated Vbeta T-cell receptor families from rheumatoid arthritis patients have yet been defined. I have designed a novel approach to the analysis of T-cell receptor transcripts which may shed new light on the repertoire of RA patients. I have focused my research on chronically-activated T-cells through the use of monoclonal antibody specific for VLA-1, a marker for chronically-activated T-cells. I also have attempted to eliminate much of the potential variability associated with PCR use in previous studies by utilizing anchor PCR (sPCR |
